Is pathological upstaging to T3a renal cell carcinoma associated with a similar prognosis to non-upstaged pathologic T3a disease? A multicenter analysis.
Authors: Ryan Nasseri, Kevin Hakimi, Jonathan Afari, Ava Saidian, Ricardo Autorino, Brian R. Lane, Michele Marchioni, Dattatraya H Patil, Chandru Sundaram, Hajime Tanaka, Francesco Porpiglia, Sabrina L. Noyes, James R Porter, Viraj A. Master, Andrea Minervini, Umberto Capitanio, Francesco Montorsi, Ithaar H Derweesh
Journal: Journal of Clinical Oncology (2023)

656 Background: Pathological upstaging to T3a disease may occur following radical (RN) or partial nephrectomy (PN) for patients with T1/T2 renal cell carcinoma (RCC). While a number of studies have demonstrated increased risk of T1/T2 upstaging to pT3a compared to initial staging, a comparison of pathologically upstaged T3a RCC and T3a RCC which was not upstaged has not been performed. We sought to compare survival outcomes and predictors of outcomes in patients who underwent surgical therapy for upstaged T3a RCC versus non-upstaged pT3a RCC. Methods: We conducted a retrospective analysis of a multi-institutional dataset of patients who underwent radical (RN) or partial nephrectomy (PN) with final pathologic stage of pT3a. Patients were classified as being upstaged (US) from cT1 or cT2 or non-upstaged (NUS) with cT3a disease. Primary outcome was Overall Survival (OS)/all-cause mortality (ACM). Secondary outcomes were Cancer-Specific Survival (CSS)/Cancer-Specific Mortality (CSM), and Recurrence-Free survival (PFS)/Recurrence. Multivariable Cox regression analysis (MVA) were conducted for predictors of mortality outcomes and Kaplan Meier Analyses (KMA) were conducted to elucidate survival outcomes comparing US and NUS groups. Results: We analyzed 879 patients [US 691 (cT1 389/cT2 302); NUS 188; median follow-up 48 months). NUS had significantly greater tumor size (9.3 vs. US 7.3 cm, p&lt;0.001), but no difference in positive surgical margins (6.9% vs. 3.9%, p=0.16). MVA for ACM revealed RN (HR 4.35, p&lt;0.001), clear-cell RCC (HR 2.38, p&lt;0.001), and positive surgical margin (HR 2.24, p=0.023) were independently associated, while upstaging status was not (p=0.78). MVA for CSM demonstrated age (HR 1.04, p=0.024) and positive margin (HR 5.28, p=0.029) were independently associated, while upstaging status was not (p=0.14). MVA for recurrence revealed positive margin (HR 6.7, p=0.003) and NUS (HR 3.85, p=0.001) to be associated with increased risk. KMA Comparing NUS and US groups, revealed no difference in 5-year OS (57% NUS vs. US 56%, p=0.38), and worsened 5-year CSS (NUS 66% vs. US 75%, p=0.04) and 5-year RFS (NUS 60% vs. US 84%, p&lt;0.001). Conclusions: Pathologic upstaging to T3a RCC was associated with a lower risk of recurrence compared to non-pathologically upstaged T3a RCC; nonetheless in our analysis upstaging status was not independently associated with increased risk of cancer-specific or overall mortality in T3a RCC. Our findings also highlight the importance of complete surgical resection in the setting of T3a disease and should prompt consideration of intensified follow up, aggressive re-salvage resection and use of adjuvant therapy.